一项全基因组关联研究确定了位于10号染色体p14区域和8号染色体q23.3区域的结直肠癌易感基因座。
A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3.
作者信息
Tomlinson Ian P M, Webb Emily, Carvajal-Carmona Luis, Broderick Peter, Howarth Kimberley, Pittman Alan M, Spain Sarah, Lubbe Steven, Walther Axel, Sullivan Kate, Jaeger Emma, Fielding Sarah, Rowan Andrew, Vijayakrishnan Jayaram, Domingo Enric, Chandler Ian, Kemp Zoe, Qureshi Mobshra, Farrington Susan M, Tenesa Albert, Prendergast James G D, Barnetson Rebecca A, Penegar Steven, Barclay Ella, Wood Wendy, Martin Lynn, Gorman Maggie, Thomas Huw, Peto Julian, Bishop D Timothy, Gray Richard, Maher Eamonn R, Lucassen Anneke, Kerr David, Evans D Gareth R, Schafmayer Clemens, Buch Stephan, Völzke Henry, Hampe Jochen, Schreiber Stefan, John Ulrich, Koessler Thibaud, Pharoah Paul, van Wezel Tom, Morreau Hans, Wijnen Juul T, Hopper John L, Southey Melissa C, Giles Graham G, Severi Gianluca, Castellví-Bel Sergi, Ruiz-Ponte Clara, Carracedo Angel, Castells Antoni, Försti Asta, Hemminki Kari, Vodicka Pavel, Naccarati Alessio, Lipton Lara, Ho Judy W C, Cheng K K, Sham Pak C, Luk J, Agúndez Jose A G, Ladero Jose M, de la Hoya Miguel, Caldés Trinidad, Niittymäki Iina, Tuupanen Sari, Karhu Auli, Aaltonen Lauri, Cazier Jean-Baptiste, Campbell Harry, Dunlop Malcolm G, Houlston Richard S
机构信息
Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London WC2A 3PX, UK.
出版信息
Nat Genet. 2008 May;40(5):623-30. doi: 10.1038/ng.111. Epub 2008 Mar 30.
To identify colorectal cancer (CRC) susceptibility alleles, we conducted a genome-wide association study. In phase 1, we genotyped 550,163 tagSNPs in 940 familial colorectal tumor cases (627 CRC, 313 high-risk adenoma) and 965 controls. In phase 2, we genotyped 42,708 selected SNPs in 2,873 CRC cases and 2,871 controls. In phase 3, we evaluated 11 SNPs showing association at P < 10(-4) in a joint analysis of phases 1 and 2 in 4,287 CRC cases and 3,743 controls. Two SNPs were taken forward to phase 4 genotyping (10,731 CRC cases and 10,961 controls from eight centers). In addition to the previously reported 8q24, 15q13 and 18q21 CRC risk loci, we identified two previously unreported associations: rs10795668, located at 10p14 (P = 2.5 x 10(-13) overall; P = 6.9 x 10(-12) replication), and rs16892766, at 8q23.3 (P = 3.3 x 10(-18) overall; P = 9.6 x 10(-17) replication), which tags a plausible causative gene, EIF3H. These data provide further evidence for the 'common-disease common-variant' model of CRC predisposition.
为了识别结直肠癌（CRC）的易感等位基因，我们开展了一项全基因组关联研究。在第一阶段，我们对940例家族性结直肠肿瘤病例（627例CRC、313例高危腺瘤）和965例对照进行了550,163个标签单核苷酸多态性（tagSNP）的基因分型。在第二阶段，我们对2,873例CRC病例和2,871例对照进行了42,708个选定SNP的基因分型。在第三阶段，我们在4,287例CRC病例和3,743例对照中对在第一和第二阶段联合分析中显示P < 10(-4)关联的11个SNP进行了评估。两个SNP被推进到第四阶段基因分型（来自八个中心的10,731例CRC病例和10,961例对照）。除了先前报道的8q24、15q13和18q21 CRC风险位点外，我们还发现了两个先前未报道的关联：位于10p14的rs10795668（总体P = 2.5 x 10(-13)；重复验证P = 6.9 x 10(-12)），以及位于8q23.3的rs16892766（总体P = 3.3 x 10(-18)；重复验证P = 9.6 x 10(-17)），其标记了一个可能的致病基因EIF3H。这些数据为CRC易感性的“常见疾病-常见变异”模型提供了进一步的证据。
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